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Journal of Clinical Medicine Feb 2023(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have... (Review)
Review
(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have assessed the pathological characteristics and outcomes of biopsy-proven kidney IRAEs. (2) Methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane for case reports, case series, and cohort studies for patients with biopsy-proven kidney IRAEs. All data were used to describe pathological characteristics and outcomes, and individual-level data from case reports and case series were pooled to analyze risk factors associated with different pathologies and prognoses. (3) Results: In total, 384 patients from 127 studies were enrolled. Most patients were treated with PD-1/PD-L1 inhibitors (76%), and 95% presented with acute kidney disease (AKD). Acute tubulointerstitial nephritis/acute interstitial nephritis (ATIN/AIN) was the most common pathologic type (72%). Most patients (89%) received steroid therapy, and 14% (42/292) required RRT. Among AKD patients, 17% (48/287) had no kidney recovery. Analyses of pooled individual-level data from 221 patients revealed that male sex, older age, and proton pump inhibitor (PPI) exposure were associated with ICI-associated ATIN/AIN. Patients with glomerular injury had an increased risk of tumor progression (OR 2.975; 95% CI, 1.176, 7.527; = 0.021), and ATIN/AIN posed a decreased risk of death (OR 0.164; 95% CI, 0.057, 0.473; = 0.001). (4) Conclusions: We provide the first systematic review of biopsy-proven ICI-kidney IRAEs of interest to clinicians. Oncologists and nephrologists should consider obtaining a kidney biopsy when clinically indicated.
PubMed: 36835884
DOI: 10.3390/jcm12041349 -
Radiation Oncology (London, England) Feb 2023This study aimed to evaluate and conduct a meta-analysis on the efficacy and safety of proton beam therapy (PBT) for rhabdomyosarcoma (RMS). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate and conduct a meta-analysis on the efficacy and safety of proton beam therapy (PBT) for rhabdomyosarcoma (RMS).
METHODS
We searched for articles using PubMed, Embase, Cochrane Library, and Web of Science databases from their inception to December 22, 2022. Two researchers independently screened literature and extracted data. Statistical analyses were performed using STATA version 14.0.
RESULTS
We got 675 candidate articles, of which 11 studies were included in our study according to the inclusion and exclusion criteria. Of the 544 RMS patients who received PBT. The local control (LC) rate at 1, 2, 3, 4, and 5 years were 96% (95% confidence interval (CI) 0.91-1.01), 93% (95% CI 0.86-1.00), 78% (95% CI 0.71-0.85), 85% (95% CI 0.78-0.92), and 84% (95% CI 0.74-0.95), respectively. The progression-free survival (PFS) rate at 1, 2, 3, 4, and 5 years were 82% (95% CI 0.72-0.92), 73% (95% CI 0.61-0.84), 63% (95% CI 0.47-0.79), 64% (95% CI 0.54-0.74), and 76% (95% CI 0.59-0.94), respectively. The overall survival (OS) rate at 1, 2, 3, 4, and 5 years were 93% (95% CI 0.86-1.00), 85% (95% CI 0.76-0.95), 80% (95% CI 0.63-0.96), 71% (95% CI 0.62-0.80), and 82% (95% CI 0.71-0.94), respectively. Acute and late toxicities were mainly grades 1 to 2 in all studies.
CONCLUSION
As an advantageous RT technique, PBT is an emerging option for patients with RMS, particularly children and adolescents patients. The data showed that PBT is a feasible, safe, and effective modality for RMS, showing promising LC, OS, PFS, and lower acute and late toxicities. PROSPERO registration number: CRD42022329154.
Topics: Adolescent; Child; Humans; Proton Therapy; Databases, Factual; Progression-Free Survival; Research Design; Rhabdomyosarcoma
PubMed: 36805784
DOI: 10.1186/s13014-023-02223-6 -
Scientific Reports Feb 2023Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in... (Meta-Analysis)
Meta-Analysis
Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in clinical practice, mainly for ulcer stress prophylaxis. In this systematic review and meta-analysis we evaluated the association between the use of PPIs in the management of AP and various clinical outcomes. We conducted the systematic research in six databases without restrictions on January 24th, 2022. We investigated adult patient with AP, who were treated with PPI compared to conventional therapy. The pooled odds ratios, mean differences, and corresponding 95% confidence intervals were calculated with random effect model. We included six RCTs and three cohort studies, consisting of 28,834 patients. We found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI treatment. PPI use was associated with a higher risk of GI bleeding, however this finding could be due to the patients' comorbid conditions. We found no significant difference in the rates of 7-day mortality, length of hospital stay, and acute respiratory distress syndrome between the groups. The available data on this topic are limited; therefore, further well designed RCTs are needed to evaluate the potential benefits and adverse effects of PPIs in AP.
Topics: Adult; Humans; Proton Pump Inhibitors; Acute Disease; Pancreatitis; Peptic Ulcer; Gastrointestinal Hemorrhage
PubMed: 36797320
DOI: 10.1038/s41598-023-29939-5 -
Frontiers in Immunology 2023Gut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Gut microbiota can significantly affect the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. Recently, antibiotics were shown to decrease survival rate of patients treated by ICIs. Proton pump inhibitors (PPIs) can indeed modulate microbiota's diversity, therefore altering ICIs response. A meta-analysis was performed based on published data to verify this hypothesis.
METHODS
In this study, over 41 publications, exploring the impact of concomitant PPI treatment on outcomes of ICI-treated patients, were analyzed. Evaluated endpoints were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) with a 95% confidence interval (CI) were reported in ICIs in PPI users versus non-PPI users. Subgroup analyses were performed to minimize the impact of study heterogeneity and to investigate the influence of PPI on the different groups of interest. There was no evidence of publication bias for OS and PFS analysis in subgroup analysis.
RESULTS
Forty-one studies were included in the meta-analysis, including a total of 20,042 patients. OS of patients receiving ICIs was negatively correlated in patients concomitantly treated with PPI (HR=1.37; 95%CI, 1.23-1.52). PFS of cancer patients receiving ICIs was also negatively correlated with PPI treatment (HR=1.28; 95%CI, 1.15-1.42). PPI and ICI use was associated with worst OS and PFS not only for non-small-cell lung cancer (NSCLC) or urothelial cancer patients but also for patients treated with anti PD-1 (OS) and anti PD-L1 (OS and PFS) immunotherapies when administered in non-first line and when PPI was received as baseline treatment or in 60 days before ICI initiation. PPI and ICI use also showed the worst OS and PFS for patients from Europe and Asia.
CONCLUSION
This meta-analysis suggests that PPI treatment leads to significantly worse outcomes in advanced cancer patients treated by ICIs in terms of PFS and OS.
Topics: Humans; Proton Pump Inhibitors; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Urinary Bladder Neoplasms
PubMed: 36776847
DOI: 10.3389/fimmu.2023.1070076 -
Radiation Oncology (London, England) Feb 2023High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams... (Review)
Review
High-grade gliomas are the most common intracranial malignancies, and their current prognosis remains poor despite standard aggressive therapy. Charged particle beams have unique physical and biological properties, especially high relative biological effectiveness (RBE) of carbon ion beam might improve the clinical treatment outcomes of malignant gliomas. We systematically reviewed the safety, efficacy, and dosimetry of carbon-ion or proton radiotherapy to treat high-grade gliomas. The protocol is detailed in the online PROSPERO database, registration No. CRD42021258495. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were collected for data analysis on charged particle radiotherapy for high-grade gliomas. Until July 2022, two independent reviewers extracted data based on inclusion and exclusion criteria. Eleven articles were eligible for further analysis. Overall survival rates were marginally higher in patients with the current standard of care than those receiving concurrent intensity-modulated radiotherapy plus temozolomide. The most common side effects of carbon-ion-related therapy were grade 1-2 (such as dermatitis, headache, and alopecia). Long-term toxicities (more than three to six months) usually present as radiation necrosis; however, toxicities higher than grade 3 were not observed. Similarly, dermatitis, headache, and alopecia are among the most common acute side effects of proton therapy treatment. Despite improvement in survival rates, the method of dose-escalation using proton boost is associated with severe brain necrosis which should not be clinically underestimated. Regarding dosimetry, two studies compared proton therapy and intensity-modulated radiation therapy plans. Proton therapy plans aimed to minimize dose exposure to non-target tissues while maintaining target coverage. The use of charged-particle radiotherapy seems to be effective with acceptable adverse effects when used either alone or as a boost. The tendency of survival outcome shows that carbon ion boost is seemingly superior to proton boost. The proton beam could provide good target coverage, and it seems to reduce dose exposure to contralateral organs at risk significantly. This can potentially reduce the treatment-related dose- and volume-related side effects in long-term survivors, such as neurocognitive impairment. High-quality randomized control trials should be conducted in the future. Moreover, Systemic therapeutic options that can be paired with charged particles are necessary.
Topics: Humans; Adult; Protons; Glioma; Proton Therapy; Headache; Carbon; Alopecia; Necrosis; Dermatitis
PubMed: 36755321
DOI: 10.1186/s13014-022-02187-z -
Clinical Gastroenterology and... Aug 2023Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Eosinophilic esophagitis (EoE) can be treated by proton pump inhibitors, topical corticosteroids, or dietary measures. This study systematically assessed the efficacy of 4 major dietary treatment regimens in EoE, updating the evidence presented in a meta-analysis from 2014.
METHODS
Electronic databases such as PubMed, Scopus, and Web of Science, and other sources were searched up to September 2022 to identify studies on dietary treatment of EoE. Based on histologic remission criteria, the efficacy of these treatments was pooled and analyzed with respect to the type of dietary regimen: 6-food elimination diet (SFED), 4-food elimination diet (FFED), 1-food elimination diet (OFED), and a targeted elimination diet (TED). Clinical response rates, food sensitization, and efficacies for a pediatric subpopulation were calculated. Influencing variables on efficacies were estimated via meta-regression analyses.
RESULTS
Thirty-four studies with 1762 patients met the inclusion criteria. The overall rate of histologic remission was 53.8% (95% CI, 48.0%-59.6%), and in the individual dietary groups was 61.3% (95% CI, 53.0%-69.3%) for SFED, 49.4% (95% CI, 32.5%-66.3%) for FFED, 51.4% (95% CI, 42.6%-60.1%) for OFED, and 45.7% (95% CI, 32.0%-59.7%) for TED. Dietary regimen and patient age did not significantly affect rates of histologic remission. The overall rate of clinical response was 80.8% (95% CI, 72.3%-88.2%), with response rates of 92.8% (95% CI, 81.2%-99.6%) for SFED, 74.1% (95% CI, 49.8%-92.6%) for FFED, 87.1% (95% CI, 58.4%-99.9%) for OFED, and 69.0% (95% CI, 50.2%85.3%) for TED.
CONCLUSIONS
Dietary therapy is an effective treatment for EoE patients of any age. The current results could support a trend toward less-restrictive dietary regimens as a primary treatment option.
Topics: Child; Humans; Allergens; Diet; Elimination Diets; Eosinophilic Esophagitis; Food; Treatment Outcome
PubMed: 36731591
DOI: 10.1016/j.cgh.2023.01.019 -
Frontiers in Pharmacology 2022Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This...
Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis.
Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD). The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195). A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06-1.26, = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30-0.64, .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups. In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.
PubMed: 36703730
DOI: 10.3389/fphar.2022.1021584 -
World Journal of Gastroenterology Jan 2023Due to increasing resistance rates of () to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and...
BACKGROUND
Due to increasing resistance rates of () to different antibiotics, failures in eradication therapies are becoming more frequent. Even though eradication criteria and treatment algorithms for first-line and second-line therapy against infection are well-established, there is no clear recommendation for third-line and rescue therapy in refractory infection.
AIM
To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory infection.
METHODS
A systematic search of available rescue treatments for refractory infection was conducted on the National Library of Medicine's PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of infection rescue therapies were included.
RESULTS
Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy, and 21 of these were selected for analysis of mean eradication rate as third-line treatment. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple-therapy as third-line treatment, mean eradication rates of 81.6% and 84.4%, 79.4% and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in intention-to-treat (ITT) and per-protocol (PP) analysis, respectively. For third-line quadruple therapy, mean eradication rates of 69.2% and 72.1% were found for bismuth quadruple therapy (BQT), 88.9% and 90.9% for bismuth quadruple therapy, three-in-one, Pylera (BQT-Pylera), and 61.3% and 64.2% for non-BQT) in ITT and PP analysis, respectively. For rifabutin-, sitafloxacin-, levofloxacin-, or metronidazole-based triple therapy as rescue therapy, mean eradication rates of 75.4% and 78.8%, 79.4 and 81.5%, 55.7% and 60.6%, and 62.0% and 63.0% were found in ITT and PP analysis, respectively. For quadruple therapy as rescue treatment, mean eradication rates of 76.7% and 79.2% for BQT, 84.9% and 87.8% for BQT-Pylera, and 61.3% and 64.2% for non-BQT were found in ITT and PP analysis, respectively. For susceptibility-guided therapy, mean eradication rates as third-line and rescue treatment were 75.0% in ITT and 79.2% in PP analysis.
CONCLUSION
We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile. In regions with known resistance to macrolides or unavailability of bismuth, rifabutin-based triple therapy is recommended.
Topics: Humans; Helicobacter Infections; Anti-Bacterial Agents; Metronidazole; Helicobacter pylori; Bismuth; Levofloxacin; Proton Pump Inhibitors; Drug Therapy, Combination; Macrolides; Drug Resistance, Bacterial; Tetracycline; Rifabutin
PubMed: 36687120
DOI: 10.3748/wjg.v29.i2.390 -
International Journal of Molecular... Jan 2023The suitability of the high-sensitivity modified Glasgow Prognostic Score (HS-mGPS) in cancer patients remains unknown. We performed a systematic database search from 1... (Meta-Analysis)
Meta-Analysis Review
The suitability of the high-sensitivity modified Glasgow Prognostic Score (HS-mGPS) in cancer patients remains unknown. We performed a systematic database search from 1 January 2010 to 30 September 2022, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Selected studies reported the HS-mGPS and survival outcomes in cancer patients. The association between the HS-mGPS and survival outcomes was evaluated using a random-effects model and expressed as pooled hazard ratios (HRs) with 95% CIs. This meta-analysis evaluated 17 studies with a total of 5828 cancer patients. A higher HS-mGPS was found to be associated with an adverse OS (HR = 2.17; 95% CI: 1.80-2.60), DSS (HR = 3.81; 95% CI: 2.03-7.17), and DFS (HR = 1.96; 95% CI: 1.48-2.58; all ≤ 0.001). The prognostic value of the HS-mGPS for the OS trended in a consistent direction after subgrouping and sensitivity analysis. In conclusion, the HS-mGPS serves as a valid prognostic biomarker for cancer patients, with a high HS-mGPS associated with adverse survival outcomes.
Topics: Humans; Neoplasms; Prognosis; Proportional Hazards Models; Retrospective Studies
PubMed: 36674837
DOI: 10.3390/ijms24021318 -
Therapeutic Advances in Gastroenterology 2023Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) bismuth-containing quadruple therapy (BQT) for ()...
BACKGROUND AND OBJECTIVE
Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) bismuth-containing quadruple therapy (BQT) for () eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for eradication compared to BQT.
DESIGN
A systematic review and meta-analysis was conducted.
METHODS
PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT BQT to eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness.
RESULTS
A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% 85.1%, RR = 1.01, 95% CI: 0.98-1.04; per-protocol analysis: 89.9% 89.4%, RR = 1.01, 95% CI: 0.98-1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% 34.1%, RR = 0.42, 95% CI: 0.34-0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00-1.03, = 0.07; low-quality evidence). The TSA result for eradication rate indicated that the effect was conclusive.
CONCLUSIONS
Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating , with fewer adverse effects and similar compliance.
REGISTRATION
Open Science Framework registries (No: osf.io/th4vd).
PubMed: 36644129
DOI: 10.1177/17562848221147756